Cucurbiturils are a class of macrocyclic compounds based on oligomers of glycoluril or glycoluril analogues.
“Cucurbituril” is the name given to the cyclic oligomer formed by linking six (6) glycoluril molecules via methylene bridges. However, the term “cucurbituril” has also been used, and is used in this specification, to refer to a class of compounds. To avoid confusion, the compound cucurbituril is referred to in this specification as “unsubstituted cucurbit[6]uril”.
Unsubstituted cucurbit[6]uril was first described in the literature in 1905 in a paper by R. Behrend, E. Meyer and F. Rusche (Leibigs Ann. Chem., 339, 1, 1905). The macrocyclic structure of unsubstituted cucurbit[6]uril was first described in 1981 by W. A. Freeman et. al. (“Cucurbituril”, J. Am. Chem. Soc., 103 (1981), 7367-7368). Unsubstituted cucurbit[6]uril has a chemical formula of C36H36N24O12 and is a macrocyclic compound having a central cavity.
The substituted cucurbituril decamethylcucurbit[5]uril was first synthesised and identified in 1992 by Flinn et. al. (Angew. Chem. Int. Ed. Engl., 1992, 31, 1475).
Various unsubstituted and substituted cucurbit[4 to 12]urils were synthesised by Day et. al. as described in the applicant's international patent application no. PCT/AU00/00412 (WO 00/68232), incorporated herein by reference.
WO 00/68232 describes the preparation of various cucurbit[4 to 12]urils from glycoluril, substituted glycolurils, or a mixture of glycoluril and substituted glycolurils. WO 00/68232 also describes the preparation of cucurbit[4 to 12]urils from a diether analogue of glycoluril, or a mixture of a diether analogue of glycoluril and glycoluril (Example 2 and Example 122). All the methods for preparing cucurbit[n]urils described in WO 00/68232 comprise reacting glycoluril and/or one or more glycoluril analogues to form the cucurbituril.
A class of cucurbit[4 to 20]urils and methods for preparing these cucurbit[4 to 20]urils are also described in U.S. Pat. No. 6,365,734. All the methods for preparing cucurbit[4 to 12]urils described in U.S. Pat. No. 6,365,734 comprise reacting glycoluril to form unsubstituted cucurbit[4 to 20]urils, or reacting substituted glycoluril to form substituted cucurbit[4 to 20]urils where all the units of the formula (B) as defined below making up the cucurbit[4 to 20]uril are identical.
Most of the cucurbiturils described in the prior art are unsubstituted or uniformly substituted cucurbiturils, that is, cucurbiturils where all the units of the formula (B) as defined below making up the cucurbituril are identical. The methods for preparing cucurbiturils described in WO 00/68232 can be used to prepare “variably substituted cucurbiturils” as defined below. If the methods for preparing cucurbit[n]urils described in WO 00/68232 are used to prepare “variably substituted cucurbiturils” as defined below, a large number of different variably substituted cucurbiturils are typically produced. For example, in Example 122(2) of WO 00/68232 cucurbit[s,u]urils were formed where s and u are 1,4; 2,3; 3,2; 4,1; 1,5; 2,4; 3,3; 4,2; 5,1; 1,6; 2,5; 3,4; 4,3; 5,2; 6,1.
Cucurbit[n]urils comprise a rigid central cavity with two portals to the central cavity. These portals are surrounded by polar groups and are narrower in diameter than the internal diameter of the cavity.
Cucurbit[4 to 12]urils selectively complex various molecules. For example, the central cavity selectively encapsulates gases and volatile molecules. Cucurbit[4 to 12]urils can also selectively form complexes with molecules at the polar ends of the central cavity. Cucurbit[4 to 12]urils can be used to form complexes with, and then later release, gases, volatiles, and other molecules. These properties give cucurbit[4 to 12]urils a wide variety of uses. These uses include for example:                entrapment and removal of pollutants,        use as odourisers, releasing fragrances slowly over time,        to trap unpleasant odours or toxic vapours, and        a chemical purification or separation techniques, for example, in chromatographic columns.        
It would be advantageous to provide alternative methods for preparing cucurbit[4 to 12]urils.